Explore the vast range of titles available.

BACKGROUND: Neuropathic mechanisms largely contribute to radicular Low Back Pain (LBP) and an increase in oxidative stress is recognized as one of the possible causes of nerve damage, inducing axonal degeneration and myelin degradation of nerve fibers. OBJECTIVES: We investigated whether a combination of nutraceutical supplements and oxygen-ozone (O2-O3) therapy might reduce disability and improve clinical effects of pharmacological therapy in patients with acute radicular LBP. STUDY DESIGN: This is a prospective, open-label, comparative observational study approved by the Institutional Review Board of the Sapienza University of Rome (RS 6285/2021). SETTING: Physical Medicine and Rehabilitation Unit of Sant’Andrea Hospital. METHODS: Within the scope of this study, 62 patients with acute radicular LBP diagnosed with disc herniation were assigned into 4 groups. The first group was assigned pharmacological therapy (n = 16), the second group was assigned pharmacological therapy and nutraceutical supplements (n = 15), the third group was assigned pharmacological therapy and O2-O3 therapy (n = 15), and the fourth group was assigned pharmacological therapy, nutraceutical supplements, and O2-O3therapy (n = 16). All patients who participated in the study were evaluated at the beginning of the study, 2 weeks, and 4 weeks (T2) after the beginning of treatment using the Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and 12-item Short-Form Health Survey. Opioid analgesic intake was noted from baseline to end of treatment (T2). RESULTS: In each group was observed a statistically significant difference for all measures compared to the baseline. At the T2 evaluation time between groups for the Mann-Whitney U test, a statistically significant difference was found: in the ODI scale between groups B and A (P = 0.004), groups C and A (P < 0.001), and groups D and A (P < 0.001); in the NRS-11 between groups B and A (P = 0.017), groups C and A (P = 0.002), and groups D and A (P < 0.001); in the 12-item Physical Component Summary score between groups B and A (P = 0.003), groups C and A (P = 0.002), and groups D and A (P < 0.001), while no significant differences between groups were observed in the 12-item Mental Component Summary score. The average days of opioid usage were similar in the 4 groups (8.33 in group A, 8.33 in group B, 8.33 in group C, and 8.75 in group D). However, the percentage of patients requiring adjuvant opioid therapy differed remarkably: 60% in group A, 40% in group B, 20% in group C, and 25% in group D. LIMITATIONS: A small number of patients were recruited, and we did not perform long-term follow-up. CONCLUSIONS: This study supports a multimodal approach combining nutraceutical supplements and O2-O3 therapy with pharmacological therapy in the treatment of acute radicular LBP secondary to disc herniation. The combination of neurotrophic and antioxidant therapies represents an etiopathogenetic approach, not purely symptomatic, that reduces symptomatology and avoids progression of the nerve damage. KEY WORDS: Low back pain, lumbar radicular pain, neuropathic pain, herniated disc, alpha lipoic acid, palmitoylethanolamide, myrrh, oxygen-ozone therapy, ozone, nutraceuticals

Facet joint osteoarthritis is the most prevalent source of facet joint pain and represents a significant cause of low back pain. Oxygen-ozone therapy has been shown to have positive results in acute and chronic spinal degeneration diseases and it could be a safe and efficacious alternative to traditional facet joint conservative treatments. This review article explains the interventional facet joint management with ultrasound-guided oxygen-ozone therapy, providing an anatomy/sonoanatomy overview of lumbar facet joints and summarizing the potential mechanism of action of oxygen-ozone in the treatment of facet joint osteoarthritis, not yet fully understood.

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10–16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 107, 108 or up to 109 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.

Studies reporting vaccine effectiveness against COVID-19 outcomes concentrate mainly on estimates of one single type of vaccine and variant, seldom considering waning effects. We aimed to estimate the effectiveness of the overall COVID-19 vaccination programme implemented in the Apulia region of Italy at preventing SARS-CoV-2 infections, COVID-19-related hospital admissions and deaths during alpha and delta variant dominant periods. We conducted a retrospective cohort study using electronic health records of persons 16 years and older resident in the Apulia region, assessing the effectiveness of the combined use of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines against confirmed COVID-19 infections, hospitalisations and deaths, for fully and partially vaccinated persons as well as by time since vaccination and variants. Cox regression models yielding hazard ratios were used to calculate the overall vaccination programme effectiveness. From 1 January to 1 December 2021, we included 3,530,967 eligible persons in the cohort, of whom 2,770,299 were fully vaccinated and 158,313 were COVID-19 positive at the end of the study period. The effectiveness of the programme over the entire study period for fully vaccinated persons against COVID-19 infection, hospitalisation and death were 87.69% (CI95% 87.73–88.18), 94.08% (93.58–94.54) and 95.95% (CI95% 95.26–96.54), respectively. The effectiveness against COVID-19 infection of fully vaccinated subjects during the alpha and delta period was respectively 88.20% (CI95% 87.60–99.78) and 59.31% (CI95% 57.91–60.67), against hospitalisation 93.89% (CI95% 92.67–94.90) and 88.32% (CI95% 86.50–89.90) and against death 93.83% (CI95% 91.65–95.45) and 85.91 (CI95% 79.98–90.09). The waning effects of the programme regarding COVID-19 infection during the delta period were stronger than for alpha, with 75.85% (CI95% 74.38–77.24) effectiveness after 1–2 months and 8.35% (CI95% 3.45–13.01) after 5–6 months after full vaccination. The effectiveness against hospitalisation and death during the delta period waned rapidly and at 7–8-months after the full vaccination respectively decreased to 27.67% (CI95% 7.48–43.45) and 48.47 (CI95% 53.97–34.82). Our study suggests that the COVID-19 vaccination program in Apulia was strongly protective against COVID-19 infection, hospitalisation, and death due to alpha as well as delta variants, although its effectiveness is reduced over time.

Gastric peroral endoscopic pyloromyotomy (G-POEM or POP) is an endoscopic therapeutic modality for treatment of refractory gastroparesis. Since the first case reported in 2013, there are more than 200 papers published on G-POEM. In this narrative review, we summarize the short-term and long-term outcomes and review other important studies. The technical success rate is 100% and the short-term (within 1 year) success rate is about 50–80%. The procedure time is between 50 and 70 min while the average length of hospital stay was 2–3 days. The adverse event rate was around 10%. Few patients need further intervention. Three studies showed that at the 4-year follow-up, the response to G-POEM was durable, but there was a yearly recurrence rate of 13% or more. Redo G-POEM is feasible and can be of benefit for some patients. Most of the studies showed that long duration of illness is associated with poor outcomes. However, reliable predictors for successful outcomes are still unknown. Current literature indicates G-POEM is superior to gastric electric stimulator and surgical pyloroplasty. Endoflip has been used at G-POEM to predict the outcome, but the result is very preliminary. A recent sham study confirms the short-term efficacy of G-POEM. G-POEM is safe and about 50% of patients can be discharged to home on the same day. G-POEM allows for direct biopsy of the gastric muscle, which is the location of the pacemaker cells, the interstitial cells of Cajal; therefore, G-POEM may provide a new path for further research on the pathogenesis of gastroparesis.

BackgroundBET inhibitors have been tested in several clinical trials where, despite encouraging preclinical results, substantial clinical benefit in monotherapy remains limited. This work illustrates the translational challenges and reports new data around the novel BET inhibitor, BI 894999. At clinically achievable concentrations, mechanistic studies were carried out to study pathway modulation and rational drug combinations.MethodsBRD-NUT fusions are oncogenic drivers in NUT carcinoma (NC). The effects of BI 894999 on proliferation, chromatin binding and pathway modulation were studied in NC in vitro. These studies were complemented by efficacy studies either as a single agent or in combination with the clinical p300/CBP inhibitor CCS1477.ResultsBased on the modelling of preclinical and clinical data, we proposed and implemented a new clinical scheduling regimen. This led to plasma levels sufficient to fully dislodge BRD-NUT from chromatin and to sustained and pronounced pharmacodynamic (PD) modulation of HEXIM1 and HIST2H2BF. Platelet counts in patient blood samples were improved compared to previous schedules. Rational combination studies of BI 894999 performed at clinically meaningful concentrations led to tumour regressions in all NC xenograft models tested.ConclusionsBI 894999 holds significant potential as a combination drug and CCS1477 p300/CBP inhibitor is a promising partner for future clinical trials.

This work aimed to evaluate phenotypically and genotypically the colistin susceptibility of 85 Salmonella Infantis strains isolated in Italy from the broiler production chain, and to apply a whole-genome approach for the determination of genes conferring antimicrobial resistance (AMR). All isolates were tested by the broth microdilution method to evaluate the colistin minimum inhibitory concentrations (MICs). A multiplex PCR was performed in all isolates for the screening of mcr-1, mcr-2, mcr-3 mcr-4, mcr-5 genes and whole-genome sequencing (WGS) of six S. Infantis was applied. Three out of 85 (3.5%) S. Infantis strains were colistin resistant (MIC values ranged from 4 to 8 mg/L) and mcr-1 positive. The mcr-1.1 and mcr-1.2 variants located on the IncX4 plasmid were detected in three different colistin-resistant isolates. The two allelic variants showed identical sequences. All six isolates harbored blaCTXM-1, aac(6′)-Iaa and gyrA/parC genes, mediating, respectively, beta-lactam, aminoglycoside and quinolone resistance. The pESI-megaplasmid carrying tet(A) (tetracycline resistance), dfrA1, (trimethoprim resistance) sul1, (sulfonamide resistance) and qacE (quaternary ammonium resistance) genes was found in all isolates. To our knowledge, this is the first report of the mcr-1.2 variant described in S. Infantis isolated from broilers chickens. Our results also showed a low prevalence of colistin- resistance, probably due to a reduction in colistin use in poultry. This might suggest an optimization of biosecurity control both on farms and in slaughterhouses.

The spread of resistant bacteria from livestock to the food industry promoted an increase of alternative poultry production systems, such as organic and antibiotic-free ones, based on the lack of antimicrobial use, except in cases in which welfare is compromised. We aimed to investigate the antibiotic susceptibility of commensal Escherichia coli isolated from organic, antibiotic-free, and conventional broiler farms and slaughterhouses toward several antimicrobials critically important for human health. To assess antimicrobial susceptibility, all E. coli isolates and extended spectrum beta-lactamase (ESBL) E. coli were analysed by the microdilution method. The prevalence of tigecycline, azithromycin and gentamicin E. coli-resistant strains was highest in organic samplings. Conversely, the lowest prevalence of resistant E. coli strains was observed for cefotaxime, ceftazidime and ciprofloxacin in organic systems, representing a significant protective factor compared to conventional systems. All E. coli strains were colistin-susceptible. Contamination of the external environment by drug-resistant bacteria could play a role in the presence of resistant strains detected in organic systems. Of interest is the highest prevalence of cephalosporin resistance of E. coli in conventional samplings, since they are not permitted in poultry. Our results suggest that monitoring of antibiotic resistance of the production chain may be helpful to detect “risks” inherent to different rearing systems.

Primary open angle glaucoma (POAG) is defined as a “genetically complex trait”, where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more “Mendelian” forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.

In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with costefficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making. We describe the efforts of the Innovative Medicines Initiative consortium CANCER-ID (http:// www.cancer-id.eu) for comparing different technologies for ccfDNA purification, quantification, and characterization in a multicenter setting. To this end, in-house generated mononucleosomal DNA (mnDNA) from lung cancer cell lines carrying known TP53 mutations was spiked in pools of plasma from healthy donors generated from 2 different blood collection tubes (BCTs). ccfDNA extraction was performed at 15 partner sites according to their respective routine practice. Downstream analysis of ccfDNA with respect to recovery, integrity, and mutation analysis was performed centralized at 4 different sites. We demonstrate suitability of mnDNA as a surrogate for ccfDNA as a process quality control from nucleic acid extraction to mutation detection. Although automated extraction protocols and quantitative PCR-based quantification methods yielded the most consistent and precise results, some kits preferentially recovered spiked mnDNA over endogenous ccfDNA. Mutated TP53 fragments derived from mnDNA were consistently detected using both next-generation sequencing-based deep sequencing and droplet digital PCR independently of BCT. This comprehensive multicenter comparison of ccfDNA preanalytical and analytical work flows is an important contribution to establishing evidence-based guidelines for clinically feasible (pre)analytical work flows.